Cardiac valve, system and method

ABSTRACT

A cardiac valve with a support frame having a first end member and a second end member opposing the first end member in a substantially fixed distance relationship, and a cover extending over the support frame to allow for unidirectional flow of a liquid through the valve.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.14/084,088, filed Nov. 19, 2013; which is a continuation of U.S.application Ser. No. 13/214,520 filed Aug. 22, 2011; which is acontinuation of U.S. application Ser. No. 12/508,369 filed Jul. 23,2009, now U.S. Pat. No. 8,002,824; which is a continuation of U.S.application Ser. No. 10/933,088, filed Sep. 2, 2004, now U.S. Pat. No.7,566,343; the contents of each are incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

Not Applicable

FIELD OF THE INVENTION

The present invention relates generally to apparatus, systems, andmethods for use in a lumen; and more particularly to cardiac valves,systems, and methods for use in the vasculature system.

BACKGROUND OF THE INVENTION

Diseases of the heart valves are grouped according to which valve(s) areinvolved and the way that blood flow is disrupted. The most common valveproblems occur in the mitral and aortic valves. Diseases of thetricuspid and pulmonary valves are fairly rare.

The aortic valve regulates the blood flow from the heart's leftventricle into the aorta. The aorta is the main vessel that suppliesoxygenated blood to the rest of the body. Diseases of the aorta can havea significant impact on an individual. Examples of such diseases includeaortic regurgitation and aortic stenosis.

Aortic regurgitation is also called aortic insufficiency or aorticincompetence. It is a condition in which blood flows backward from awidened or weakened aortic valve into the left ventricle of the heart.In its most serious form, aortic regurgitation is caused by an infectionthat leaves holes in the valve leaflets. Symptoms of aorticregurgitation may not appear for years. When symptoms do appear, it isbecause the left ventricle must work harder as compared to anuncompromised ventricle to make up for the backflow of blood. Theventricle eventually gets larger and fluid backs up.

Aortic stenosis is a narrowing or blockage of the aortic valve. Aorticstenosis occurs when the valve leaflets of the aorta become coated withdeposits. The deposits change the shape of the leaflets and reduce bloodflow through the valve. The left ventricle has to work harder ascompared to an uncompromised ventricle to make up for the reduced bloodflow. Over time, the extra work can weaken the heart muscle.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1D illustrate an embodiment of a valve in perspective view.

FIGS. 2A-2B illustrate another embodiment of a valve in perspectiveview.

FIGS. 3A and 3B illustrate another embodiment of a valve in perspectiveview.

FIGS. 4A and 4B illustrate another embodiment of a valve in perspectiveview.

FIG. 5 illustrates an embodiment of a system that includes a valve.

FIG. 6 illustrates an embodiment of a system that includes a valve.

FIG. 7 illustrates an embodiment of a system that includes a valve.

DETAILED DESCRIPTION

Embodiments of the present invention are directed to an apparatus,system, and method for cardiac valve replacement and/or augmentation.For example, the apparatus can include a cardiac valve that can be usedto replace an incompetent valve in a body lumen. Embodiments of thecardiac valve can include a support frame and cover that can beimplanted through minimally-invasive techniques into a body lumen, suchas an artery or a vein. In one example, embodiments of the presentinvention may help to augment or replace the function of a cardiac valveof individuals having heart valve disease.

The Figures herein follow a numbering convention in which the firstdigit or digits correspond to the drawing Figure number and theremaining digits identify an element or component in the drawing.Similar elements or components between different Figures may beidentified by the use of similar digits. For example, 110 may referenceelement “10” in FIG. 1, and a similar element may be referenced as 210in FIG. 2. As will be appreciated, elements shown in the variousembodiments herein can be added, exchanged, and/or eliminated so as toprovide any number of additional embodiments of valve.

Various embodiments of the invention are illustrated in the figures.Generally, the cardiac valve can be implanted within the fluidpassageway of a body lumen, such as for replacement of a cardiac valvestructure within the body lumen (e.g., an aortic valve at the aorticroot), to regulate the flow of a bodily fluid through the body lumen ina single direction.

FIGS. 1A and 1B illustrate one embodiment of a cardiac valve 100. FIGS.1A and 1B provide a perspective illustration of valve 100 in an openconfiguration (FIG. 1A) and a closed configuration (FIG. 1B). FIGS. 1Cand 1D provide a sectional view of FIGS. 1A and 1B, respectively, tomore clearly illustrate the embodiment of the cardiac valve 100.

Cardiac valve 100 includes a support frame 102 and a cover 104. Thesupport frame 102 includes an outer surface 106 and an inner surface108. The support frame 102 further includes a first end member 110 and asecond end member 112 opposing the first end member 110. In oneembodiment, the first end member 110 and the second end member 112 arein a substantially fixed distance relationship 114. As used herein, asubstantially fixed distance relationship 114 indicates a fixed distancebetween the members 110 and 112 that may include variations of the fixeddistance relationship inherently resulting from the manufacture of thearticles of the present invention. In addition, the substantially fixeddistance relationship 114 need not be consistent around thecircumference of the cardiac valve 100. For example, the substantiallyfixed distance relationship 114 can be varied up to a predeterminedpercentage of an average valve diameter of the substantially fixeddistance relationship 114. In one embodiment, the predeterminedpercentage can be up to seventy (70) percent (%).

The support frame 102 further includes an open frame configuration inwhich the first end member 110 and the second end member 112 are closedrings that define a sequence of convex curves 116 and concave curves118. In one embodiment, the sequence of convex curves 116 and concavecurves 118 are arranged such that the first end member 110 and thesecond end member 112 provide mirror images of each other set apart bythe substantially fixed distance relationship 114. In anotherembodiment, the sequence of convex curves 116 and concave curves 118 arearranged such that the first end member 110 and the second end member112 are substantially parallel. In an alternative embodiment, thesequence of convex curves 116 and concave curves 118 are arranged suchthat the relative position of the first end member 110 and the secondend member 112 can have a variation from about zero (0) percent to abouttwo hundred (200) percent variation as compared to an average distanceor a preselected distance between the members 110 and 112. In oneembodiment, the valve can be about twenty (20) to eighty (80) percent.As will be appreciated, the selection of these percentage values can bebased on the anatomical location into which the valve is to be placed.

As illustrated in FIGS. 1A and 1B, the sequence of convex curves 116 andconcave curves 118 of the first and second end members 110 and 112 cantransition between each other with a uniform radius of curvature foreach of the convex curves 116 and concave curves 118. Alternatively, thesequence of convex curves 116 and concave curves 118 transition betweeneach other in a non-uniform manner. For example, the convex curves 116can have a radius of curvature that is different (e.g., smaller) thanthe radius of curvature for the concave curves 118 (FIGS. 2A and 2B).Further, the shape and relationship of the convex curves 116 and concavecurves 118 for each of the first end member 110 and the second endmember 112 need not be symmetrical relative to each other, rather theymay provide for a non-symmetrical relationship, which may vary aroundthe circumference.

The support frame 102 can further include cross-members 120 coupled tothe first end member 110 and the second end member 112. In oneembodiment, cross-members 120 help to maintain the first end member 110and the second end member 112 in the substantially fixed distancerelationship 114. In one embodiment, the cross-members 120 can include across-sectional shape and can be formed from the same or similarmaterials as the end members 110 and 112, as discussed herein. Inaddition, the cross-members 120 can include any number ofconfigurations, including linear configurations in which cross member120 are arranged in parallel relative to other cross-members 120. Otherconfigurations include, but are not limited to, curved configurations,configurations including one or more bends in the cross member 120, andconfigurations that include coil configurations. Other configurationsare also possible. In addition, the cross-members 120 can furtherinclude additional members spanning between the cross-members 120 and/orthe end members 110 and 112, as will be discussed herein.

The support frame 102 can be formed from a wide variety of materials andin a wide variety of configurations. Generally, support frame 102 canhave a unitary structure with an open frame configuration. For example,the open frame configuration can include frame members (e.g., first endmember 110 and a second end member 112, cross-members 120) that defineopenings 124 through the support frame 102. The support frame 102 canalso be self-expanding. Examples of self-expanding frames include thoseformed from temperature-sensitive memory alloy which changes shape at adesignated temperature or temperature range. Alternatively, theself-expanding frames can include those having a spring-bias. Inaddition, the support frame 102 can have a configuration that allows theframe 102 to be radially expandable through the use of a ballooncatheter.

While the support frame 102 illustrated herein is shown having acircular configuration, other configurations are also possible. Forexample, the support frame 102 can also include an ellipticalconfiguration, or other configurations that can accommodate thephysiological structure in which the support frame 102 is to be placed.In addition, the support frame 102 is illustrated as having linear orlong curved members, it will be appreciated that the support frame 102and/or the cross-members 120 can have a configuration that allows thesupport frame 102 and/or the cross-members 120 to be flexible. Examplesof such configurations include those that are zigzag and/or serpentineso as to allow the frame to be radially compressible. As such, thepresent invention should not be limited to the illustration of thesupport frame 102.

The support frame 102 can also provide sufficient contact and expansionforce with the surface of a body lumen wall to encourage fixation of thevalve 100 and to prevent retrograde flow within the body lumen.Anchoring elements (e.g., barbs) can also be included with valve 100, aswill be discussed herein.

The members (e.g., first end member 110 and a second end member 112,cross-members 120) forming support frame 102 can include a variety ofcross-sectional shapes and dimensions. For example, cross-sectionalshapes for the members 122 can include, but are not limited to,circular, tubular, I-shaped, T-shaped, oval, and triangular. The memberscan also have a single cross-sectional shape (e.g., all members ofsupport frame 102 can have a circular cross-sectional shape). In anadditional embodiment, the members of the support frame 102 can includetwo or more cross-sectional shapes (e.g., a first cross-sectional shapefor both the first end member 110 and a second end member 112, and asecond cross-sectional shape for the cross-members 120).

The support frame 102 can be formed from any number of materials. Forexample, the support frame 102 can be formed from a biocompatible metal,metal alloy, polymeric material, or combination thereof. As discussedherein, the support frame 102 can be self-expanding or balloonexpandable. Examples of suitable materials for the support frame 102include, but are not limited to, medical grade stainless steel (e.g.,316L), titanium, tantalum, platinum alloys, niobium alloys, cobaltalloys, alginate, or combinations thereof. In an additional embodiment,the support frame 102 may be formed from a shape-memory material, suchas shape memory plastics, polymers, and thermoplastic materials whichare inert in the body. Shaped memory alloys having superelasticproperties generally made from specific ratios of nickel and titanium,commonly known as nitinol, are also possible materials. Other materialsare also possible.

Members (e.g., first end member 110 and a second end member 112, crossmembers 120) of the support frame 102 can be shaped and joined in anynumber of ways. For example, a single contiguous member can be bentaround an elongate tubular mandrel to form the end members 110 and 112of the support frame 102. The free ends of the single contiguous membercan then be welded, fused, crimped, or otherwise joined together to formthe support frame 102. In an additional embodiment, the cross-members120 can be joined to the end members 110 and 112 in a similar manner.Alternatively, the support frame 102 can be derived (e.g., laser cut,water cut) from a single tubular segment. The support frame 102 can beheat set by a method as is typically known for the material which formsthe support frame 102.

Support frame 102 and cover 104 can be expanded to provide lumen 126having any number of sizes. For example, the size of lumen 126 can bedetermined based upon the type of body lumen and the body lumen size inwhich the valve 100 is to be placed. In an additional example, there canalso be a minimum value for the width 128 for the support frame 102 thatensures that the support frame 102 will have an appropriate expansionforce against the inner wall of the body lumen in which the valve 100 isbeing placed. The support frame 102 can also include a longitudinallength 130.

In one embodiment, the support frame 102 can further include one or moreanchoring elements. For example, the one or more anchoring elements caninclude, but are not limited to, one or more barbs 132 projecting fromthe outer surface 106 of the support frame 102. The valve 100 canfurther include one or more radiopaque markers (e.g., tabs, sleeves,welds). For example, one or more portions of the valve frame 102 can beformed from a radiopaque material. Radiopaque markers can be attached toand/or coated onto one or more locations along the support frame 102.Examples of radiopaque material include, but are not limited to, gold,tantalum, and platinum. The position of the one or more radiopaquemarkers can be selected so as to provide information on the position,location and orientation of the valve 100 during its implantation.

As discussed herein, the cover 104 of the cardiac valve 100 forms valveleaflets 133 having surfaces defining a reversibly sealable opening 134for unidirectional flow of a liquid through the valve 100. For example,the cover 104 can extend across an area between the convex curves 116and the concave curves 118 of the second end member 112 to form valveleaflets 133 of the cardiac valve 100. The position and number of theconvex and concave curves 116 and 118 in the second end member 112determine the number of valve leaflets 133 of the cardiac valve 100.

For example, FIGS. 1A and 1B provide a bi-leaflet cardiac valveaccording to an embodiment of the present invention. As illustrated inFIGS. 1A and 1B, cover 104 extends across the area between a firstconvex curve 136 and a second convex curve 138 and down to the concavecurves 118 of the second end member 112 to form a first valve leaflet140 and a second valve leaflet 142.

In one embodiment, the first convex curve 136 and the second convexcurve 138 of the second end member 112 are positioned opposite eachother along a common axis 144. In this example, the common axis 144bisects support frame 102 into symmetrical portions. As a result, thefirst valve leaflet 140 and the second valve leaflet 142 each displaysubstantially the same shape, size and configuration as each other. Inan alternative embodiment, the first convex curve 136 and the secondconvex curve 138 can be positioned so that the common axis 144 dividesthe support frame 102 into non-symmetrical portions. In this embodiment,the first valve leaflet 140 and the second valve leaflet 142 can havedifferent shapes, sizes and configurations relative to each other.

In an additional embodiment, the cover 104 also extends over the firstend member 110. In contrast to the second end member 112, however, thecover 104 terminates along the convex and concave curves 116 and 118 ofthe first end member 110 so as to define an open area 146 between thesequence of convex curves 116 and concave curves 118. As will be morefully discussed below, providing the open area 146 allows the valve 100to accommodate the anatomical structures of the autologous valve beingreplaced so as to reduce any potential interference with anatomicalstructures adjacent the autologous valve (e.g., the coronary ostialocated adjacent aortic valve).

Although the embodiments in FIGS. 1A-1D illustrate and describe abi-leaflet configuration for the valve 100 of the present invention,designs employing a different number of valve leaflets are possible. Forexample, the second end member 112 can include additional convex curves116 and the concave curves 118 so as to provide support structures foradditional valve leaflets 133 (e.g., a tri-leaflet valve).

The cover 104 in conjunction with the support frame 102 defines thelumen 126 of the cardiac valve 100 for passing fluid (e.g., blood)there-through. The cover 104 further includes surfaces defining areversibly sealable opening 134 for unidirectional flow of a liquidthrough the lumen 126. For example, a portion of the first valve leaflet140 and the second valve leaflet 142 can join to form the reversiblysealable opening 134 for unidirectional flow of a liquid through thecardiac valve 100. FIGS. 1A and 1B illustrate embodiments in which thesurfaces of the cover 104 can be deflectable between a closedconfiguration (FIG. 1B) in which fluid flow through the lumen 126 can berestricted and an open configuration (FIG. 1A) in which fluid flowthrough the lumen 126 can be permitted.

The first valve leaflet 140 and the second valve leaflet 142 can moverelative the support frame 102 (i.e., the first valve leaflet 140 andthe second valve leaflet 142 are attached to and pivot along the supportframe 102). In one embodiment, the cover 104 provides sufficient excessmaterial spanning support frame 102 to allow the first valve leaflet 140and the second valve leaflet 142 to join sealing surfaces 148 at thereversibly sealable opening 134. The reversibly sealable opening 134formed by the first and second valve leaflets 140 and 142 opens andcloses in response to the fluid pressure differential across the valveleaflets 140 and 142. That is, antegrade blood flow causes the valveleaflets to open, thereby providing for unidirectional blood flowthrough the reversibly sealable opening. In contrast, retrograde bloodflow causes the valve leaflets close, thereby preventing blood flow frompassing through the reversibly sealable opening.

The first valve leaflet 140 and the second valve leaflet 142 furtherinclude arcuate edges 150 and 152 that are positioned adjacent eachother along a substantially catenary curve between the first convexcurve 136 and the second convex curve 138 of the second end member 112in the closed configuration (FIG. 1B) of valve 100. Similarly, arcuateedges 150 and 152 can form the reversibly sealable opening 134 when thevalve 100 is in the open configuration (FIG. 1A).

For example, under antegrade fluid flow (i.e., positive fluid pressure)moving from the first end member 110 towards the second end member 112of the valve 100, the first and second valve leaflets 140 and 142 canexpand toward the support frame 102 to create an opening through whichfluid is permitted to move. In one embodiment, the first valve leaflet140 and the second valve leaflet 142 can each expand to form asemi-tubular structure when fluid opens the reversibly sealable opening134. In an additional embodiment, arcuate edge 150 and 152 of valve 100can open to approximately the full inner diameter of a body lumen. Anexample of the open configuration for the valve is shown in FIG. 1A.Also as can be seen, the first and second valve leaflets 133 extend avariable distance beyond the second end member 112.

Under a retrograde fluid flow (i.e., negative fluid pressure) movingfrom the second end member 112 towards the first end member 110, thefirst and second valve leaflets 140 and 142 move away from the supportframe 102 as the valve leaflets 140 and 142 begin to close. In oneembodiment, the valve leaflets 140 and 142 include a predefined shapethat allows for the retrograde fluid flow to develop pressure on a majorsurface 154 of the first and second valve leaflets 140 and 142.

For example, the major surface 154 can have a concave shape 156 tobetter collect retrograde fluid flow to urge the first valve leaflet 140and the second valve leaflet 142 towards the closed configuration. Asfluid pressure builds, the first and second valve leaflets 140 and 142move towards each other eventually forming the reversibly sealableopening 134 (i.e., closing the valve 100), thereby restrictingretrograde fluid flow through the valve 100. As can be seen in FIGS. 1Band 1D, when the valve leaflets 140, 142 obstruct the lumen 126 of thevalve, the valve leaflets 140, 142 do not extend a variable distancebeyond the second end member 112. Also, the valve leaflets 140, 142 aresubstantially perpendicular to the longitudinal axis of the valve.

In an additional embodiment, the first valve leaflet 140 and the secondvalve leaflet 142 can include one or more support structures, where thesupport structures can be integrated into and/or onto the valve leaflets140 and 142. For example, the first valve leaflet 140 and the secondvalve leaflet 142 can include one or more support ribs having apredetermined shape. In one embodiment, the predetermined shape of thesupport ribs can include a curved bias so as to provide the first valveleaflet 140 and the second valve leaflet 142 with a curvedconfiguration. Support ribs can be constructed of a flexible materialand have dimensions (e.g., thickness, width and length) andcross-sectional shape that allows the support ribs to be flexible whenthe first valve leaflet 140 and the second valve leaflet 142 are urgedinto an open position upon experiencing sufficient blood flow pressurefrom the direction upstream from the valve, e.g., antegrade blood flow,and stiff when the first valve leaflet 140 and the second valve leaflet142 are urged into a closed position upon experiencing sufficient backflow pressure from the direction downstream from the valve, e.g.,retrograde blood flow. In an additional embodiment, support ribs canalso be attached to support frame 102 so as to impart a spring bias tothe valve leaflets 133 in either the open or the closed configuration.

In one embodiment, cover 104 used to form the valve leaflets 140 and 142can be constructed of a material sufficiently thin and pliable so as topermit radially-collapsing of the valve leaflets for delivery bycatheter to a location within a body lumen. The cover 104 can beconstructed of a biocompatible material that can be either synthetic orbiologic or a combination of synthetic and biologic biocompatiblematerial. Possible synthetic materials include, but are not limited to,expanded polytetrafluoroethylene (ePTFE), polytetrafluoroethylene(PTFE), polystyrene-polyisobutylene-polystyrene (SIBS), polyurethane,segmented poly(carbonate-urethane), polyester, polyethlylene (PE),polyethylene terephthalate (PET), silk, urethane, Rayon, Silicone, orthe like. In an additional embodiment, the synthetic material can alsoinclude metals, such as stainless steel (e.g., 316L) and nitinol. Thesesynthetic materials can be in a woven, a knit, a cast or other knownphysical fluid-impermeable or permeable configurations.

Possible biologic materials include, but are not limited to, autologous,allogeneic or xenograft material. These include explanted veins,pericardium, facia lata, harvested cardiac valves, bladder, vein wall,various collagen types, elastin, intestinal submucosa, anddecellularized basement membrane materials, such as small intestinesubmucosa (515), amniotic tissue, or umbilical vein.

As discussed herein, the cover 104 can be located over at least theouter surface 106 of the support frame 102. FIGS. 1A-1D provide oneillustration of this embodiment. As can be seen, the leaflets 133 extendfrom the portion of the cover extending over the support frame 102. Inan additional embodiment, the cover 104 can be located over at least theinner surface 108 of the support frame 102.

FIGS. 2A-2B provide a cross-sectional perspective view of cover 204extending over both an inner surface 208 and the outer surface 206 ofthe support frame 202 to form the bi-leaflet cardiac valve. In oneexample, the cover 204 can further be located over the openings 224defined by the members of the support frame 202. The cover 204 can alsobe joined to itself through the openings 224 so as to fully or partiallyencase the support frame 202.

Numerous techniques may be employed to laminate or bond the cover 204 onthe outer surface 206 and/or the inner surface 208 of the support frame202, including heat setting, adhesive welding, interlocking, applicationof uniform force and other bonding techniques. Additionally, the cover204 may be folded over the first end member 210 of the support frame 202to provide the cover 204 on both the outer surface 206 and the innersurface 208. Cover 204 can also be joined to itself and/or the membersaccording to the methods described in U.S. Patent ApplicationPublication US 2002/0178570 to Sogard et al.

The valve 200 can further include a layer of material 258 positionedbetween the cover 204 extending over the inner surface 208 and the outersurface 206 of the support frame 202. The layer of material 258 can beformed from the biocompatible material used for the cover 204. The layerof material 258, however, can be structurally different than thematerial of cover 204. For example, cover 204 can include a fluidpermeable open woven, or knit, physical configuration to allow fortissue in-growth and stabilization, whereas the layer of material 258can have a fluid impermeable physical configuration. Examples of thematerial 258 include, but are not limited to, the synthetic materialsdescribed herein. Other combinations of physical configurations for thecover 204 and the layer of material 258 are also possible.

Referring again to FIGS. 1A-1D, the support frame 102 and/or the cover104, including the valve leaflets 140 and 142, may also be treatedand/or coated with any number of surface or material treatments. Forexample, suitable bioactive agents which may be incorporated with orutilized together with the present invention may be selected from silverantimicrobial agents, metallic antimicrobial materials, growth factors,cellular migration agents, cellular proliferation agents, anti-coagulantsubstances, stenosis inhibitors, thrombo-resistant agents, antibioticagents, anti-tumor agents, anti-proliferative agents, growth hormones,antiviral agents, anti-angiogenic agents, angiogenic agents,cholesterol-lowering agents, vasodilating agents, agents that interferewith endogenous vasoactive mechanisms, hormones, their homologs,derivatives, fragments, pharmaceutical salts and combinations thereof.

In the various embodiments of the present invention, the most usefulbioactive agents can include those that modulate thrombosis, those thatencourage cellular ingrowth, throughgrowth, and endothelialization,those that resist infection, and those that reduce calcification. Forexample, coating treatments can include one or more biologically activecompounds and/or materials that may promote and/or inhibit endothelial,smooth muscle, fibroblast, and/or other cellular growth onto or into thesupport frame 102 and/or the cover 104, including the valve leaflets 140and 142. Examples of such coatings include, but are not limited to,polyglactic acid, poly-L-lactic acid, glycol-compounds, and lipidcompounds. Additionally, coatings can include medications, geneticagents, chemical agents, and/or other materials and additives. Inaddition, in embodiments having tubular members such as the tubularmember 482 illustrated in FIGS. 4A-4B, agents that limit or decreasecellular proliferation can be useful. Similarly, the support frame 102and/or the cover 104 may be seeded and covered with cultured tissuecells (e.g., endothelial cells) derived from a either a donor or thehost patient which are attached to the valve leaflets 140 and 142. Thecultured tissue cells may be initially positioned to extend eitherpartially or fully over the valve leaflets 140 and 142.

Cover 104, in addition to forming valve leaflets 140 and 142, can alsobe capable of inhibiting thrombus formation, as discussed herein.Additionally, cover 104 may either prevent or facilitate tissue ingrowththere-through, as the particular application for the valve 100 maydictate. For example, cover 104 on the outer surface 106 may be formedfrom a porous material to facilitate tissue ingrowth there-through,while cover 104 on the inner surface 108 may be formed from a materialor a treated material which inhibits tissue ingrowth.

Cells can be associated with the present invention. For example, cellsthat have been genetically engineered to deliver bioactive proteins,such as the growth factors or antibodies mentioned herein, to theimplant site can be associated with the present invention. Cells can beof human origin (autologous or allogenic) or from an animal source(xenogenic). Cells can be pre-treated with medication or preprocessedsuch as by sorting or encapsulation. The delivery media can beformulated as needed to maintain cell function and viability.

Thrombo-resistant agents associated with the valve may be selected from,but not limited to, heparin, heparin sulfate, hirudin, hyaluronic acid,chondroitin sulfate, dermatan sulfate, keratin sulfate, PPack(detropyenylalanine praline arginine chloromethylketone), lytic agents,including urokinase and streptokinase, their homologs, analogs,fragments, derivatives and pharmaceutical salts thereof.

Anti-coagulants can include, but are not limited to, D-Phe-Pro-Argchloromethyl ketone, an RGD peptide-containing compound, heparain,antithrombin compounds, platelet receptor antagonists, anti-thrombinantibodies, anti-platelet receptor antibodies, aspirin, prostaglandininhibitors, platelet inhibitors, tick antiplatelet peptides andcombinations thereof.

Antibiotic agents can include, but are not limited to, penicillins,cephalosportins, vancomycins, aminoglycosides, quinolonges, polymyxins,erythromycins, tetracyclines, chloraphenicols, clindamycins,lincomycins, sulfonamides, their homologs, analogs, derivatives,pharmaceutical salts and combinations thereof.

Anti-proliferative agents for use in the present invention can include,but are not limited to, the following: paclitaxel, sirolimus,everolimus, or monoclonal antibodies capable of blocking smooth musclecell proliferation, related compounds, derivatives, and combinationsthereof.

Vascular cell growth inhibitors can include, but are not limited to,growth factor inhibitors, growth factor receptor antagonists,transcriptional repressors, translational repressors, replicationinhibitors, inhibitory antibodies, antibodies directed against growthfactors, bifunctional molecules consisting of a growth factor and acytotoxin, bifunctional molecules consisting of a an antibody and acytotoxin.

Vascular cell growth promoters include, but are not limited to,transcriptional activators and transcriptional promoters.Anti-inflammatory agents can include, but are not limited to,dexametbasone, prednisolone, corticosterone, budesonide, estrogen,sulfasalazinemesalamne, and combinations thereof

FIGS. 3A and 3B illustrate an additional embodiment of a cardiac valve300. FIGS. 3A and 3B provide a perspective illustration of valve 300having three valve leaflets 333 in an open configuration (FIG. 3A) and aclosed configuration (FIG. 3B).

As discussed herein, cardiac valve 300 includes the support frame 302having the first end member 310 and the second end member 312 opposingthe first end member 310 in the substantially fixed distancerelationship 314. In the present example, the cover 304 of the cardiacvalve 300 forms a tri-leaflet valve having surfaces defining thereversibly sealable opening 334 for unidirectional flow of a liquidthrough the valve 300. As illustrated, FIGS. 3A and 3B provide atri-leaflet cardiac valve in which cover 304 extends across the areabetween the first convex curve 336, the second convex curve 338, and athird convex curve 364, and down to the concave curves 318 of the secondend member 312 to form the first valve leaflet 340, the second valveleaflet 342, and a third valve leaflet 366

In one embodiment, the convex curves 336, 338, and 364 can lay on acommon plane 368, as illustrated in FIGS. 3A and 3B. However, the convexcurves 336, 338, and 364 can lay need not all lay on the common plane368. It is possible that one or more of the convex curves 336, 338, and364 can lie above and/or below the common plane 368. In addition, theconvex curves 336, 338, and 364 can be positioned at equal distancesaround the second end member 312. As a result, the valve leaflets 336,338, and 364 each display substantially the same shape, size andconfiguration as each other. In an alternative embodiment, the convexcurves 336, 338, and 364 can be positioned at one or more unequaldistances around the second end member 312. In this embodiment, thevalve leaflets 336, 338, and 364 can each have different shapes, sizesand configurations relative to each other.

The cover 304 in conjunction with the support frame 302 defines thelumen 326 of the cardiac valve 300 for passing fluid (e.g., blood)there-through. The cover 304 can further include surfaces defining thereversibly sealable opening 334 for unidirectional flow of a liquidthrough the lumen 326. For example, a portion of the first valve leaflet340, the second valve leaflet 342, and the third valve leaflet 366 canjoin to form the reversibly sealable opening 334 for unidirectional flowof a liquid through the cardiac valve 300. FIGS. 3A and 3B illustrateembodiments in which the valve leaflets 340, 342, and 366 can deflectbetween a closed configuration (FIG. 3B) in which fluid flow through thelumen 326 can be restricted and an open configuration (FIG. 3A) in whichfluid flow through the lumen 326 can be permitted.

The first valve leaflet 340, the second valve leaflet 342, and the thirdvalve leaflet 366 can move relative the support frame 302 between theopen configuration and the closed configuration. As discussed, the cover304 provides sufficient excess material spanning support frame 302 toallow the valve leaflets 340, 342, and 366 to join sealing surfaces 348at a reversibly sealable opening 334. The reversibly sealable opening334 formed by the first, second, and third valve leaflets 340, 342, and366 opens and closes in response to the fluid pressure differentialacross the valve leaflets.

The valve leaflets 340, 342, and 366 each include concave surfaces 370projecting from the support frame 302 towards an arcuate edge 372projecting into the lumen 326. As discussed, the valve leaflets 340,342, and 366 can have approximately the same size and shape. The arcuateedge 372 of the valve leaflets 340, 342, and 366 can each furtherinclude a nodular interruption 374 at approximately the center 376 ofthe arcuate edge 372 to allow the edges of the leaflets 340, 342, and366 to properly meet as the valve closes.

During retrograde flow (i.e., negative fluid pressure), the valveleaflets 340, 342, and 366 can fall into the lumen to close thereversibly sealable opening 334 and support the column of fluid (e.g.,blood). During antegrade fluid flow (i.e., positive fluid pressure) thevalve leaflets 340, 342, and 366 can expand or move toward the supportframe 302 to create an opening through which fluid is permitted to move.In one embodiment, the valve leaflets 340, 342, and 366 can each expandor move to form a semi-tubular structure when fluid opens the reversiblysealable opening 334. In an additional embodiment, the valve leaflets340, 342, and 366 can include one or more support structures (e.g.,support ribs), as discussed herein.

Cover 304 can extend over at least the outer surface 306 of the supportframe 302 to form the valve leaflets of the tri-leaflet cardiac valve.Alternatively, cover 304 can also be located over at least the innersurface 308 of the support frame 302 to form the valve leaflets of thetri-leaflet cardiac valve. The cover 304 can be joined to the supportframe 302 and itself as discussed herein. In addition, the valve 300 canfurther include a layer of material 358 positioned between the cover 304extending over the inner surface 308 and the outer surface 306 of thesupport frame 302. The cover 304, including the valve leaflets 340, 342,and 366, may also be treated and/or coated with any number of surface ormaterial treatments, as discussed herein.

FIGS. 4A and 4B illustrate a further embodiment of a cardiac valve 400.FIGS. 4A and 4B provide a perspective illustration of valve 400 in anopen configuration (FIG. 4A) and a closed configuration (FIG. 4B). Asdiscussed herein, the valve 400 the support frame 402 and the cover 404that forms valve leaflets having surfaces defining a reversibly sealableopening 434 for unidirectional flow of a liquid through the valve 400.

In addition, the present embodiment further includes an elongate tubularmember 482 having a first end 484 and a second end 486. As illustrated,the elongate tubular member 482 can be positioned relative the supportframe 402 to allow the first end 484 of the member 482 to be on a firstside of the valve leaflets and the second end 486 on a second side ofthe valve leaflets. In one embodiment, the tubular member 482 can passthrough an opening in a valve leaflet, where the tubular member 482 andthe valve leaflet form a fluid tight seal. Alternatively, the tubularmember 482 passes through a region of the reversibly sealable opening434, where the leaflets seal around the tubular member 482 when they arein their closed position. As illustrated in FIGS. 4A and 4B, the tubularmember 482 can be positioned within the opening defined by the supportframe 402. In an alternative embodiment, the tubular member 482 can bepositioned outside of the support frame 402.

The tubular member 482 can allow fluid communication across the valve400 when the valve leaflet 433 are in their closed position. In oneembodiment, the tubular member 482 can allow for blood at an arterialpressure to be supplied from a region distal to the valve 400 to vesselslocated proximal the valve 400. In one embodiment, the tubular member482 can allow the valve 400 to be positioned at a more convenient and/orless-diseased location in the vasculature (e.g., the aorta) while stillallowing blood at arterial pressure to be supplied to the appropriatecoronary arteries (e.g., via the coronary ostium).

The tubular member 482 can include any number of physicalconfigurations. For example, as shown in FIG. 4A, the tubular member 482can include a predetermined length and a predetermined bend 483 to allowthe second end 486 of the tubular member 482 to be implanted in adesired location. Examples of such locations include, but are notlimited to, a coronary ostium. The predetermined length of the tubularmember 482 can be in a range from 10 mm to 50 mm, where the length ofthe tubular member 482 will be determined based on where the valve 400is being implanted along with the patient's individual physiologicalparameters and measurements.

As will be appreciated, the valve 400 can include more than one tubularmember 482. For example, the valve 400 can include two or more tubularmembers 482, each tubular member supplying a coronary artery of thepatient's vasculature. In addition, each of the tubular members 482 canhave similar or distinct physical characteristics (e.g., length,inner/outer diameter, predetermined shape). In one embodiment, each ofthe tubular members 482 can further include one or more radiopaque marksto allow each tubular member 482 to be uniquely identified.

The tubular member 482 can further include a predetermined shape. In oneembodiment, the predetermined shape can be determined by the anatomicallocation in which the valve 400 is being placed along with theanatomical location in which the second end 486 of the tubular member482 is to be placed. As illustrated in FIGS. 4A and 4B, the tubularmember 482 can include combinations of linear and bend portions impartedinto the tubular member 484 (e.g., the predetermined bend 483illustrated in FIG. 4B).

The tubular member 482 can be constructed of a material havingsufficient flexibility so as to permit the second end 486 of the tubularmember 482 to remain positioned in its proper anatomical location withinthe patient, while also being flexible enough to allow the first end 484to move radially with the valve leaflet. The tubular member 482 can beconstructed of a biocompatible material that can be either synthetic orbiologic. Examples of these materials include those discussed herein forthe cover 404. In addition, the material used in the construction of thetubular member 484 can be the same or a different material used for theconstruction of the cover 404. The tubular member 482 can also include astent support structure to help maintain a predetermined shape of thetubular member 482.

The tubular member 482 further includes an inner diameter 488 and outerdiameter 490. The inner diameter 488 can be in a range of 2.0 mm to 5.5mm. Alternatively, the inner diameter 488 can be in a range of 3.0 mm to4.5 mm. In one embodiment, the dimension of the inner diameter 488 willtypically be a function of the volume of fluid flow that is desired tomove through the tubular member 484. The dimension for the outerdiameter 490 will be dependent upon the wall thickness of the tubularmember 482 required to provide proper flexibility and rigidity tomaintain its position once placed in the patient.

The embodiments of the valve of the present invention can be formed inany number of ways. For example, a support frame and a cover are bothprovided for forming the cardiac valve. In the present example, thecover can have a cylindrical shape of essentially uniform innerdiameter, where the inner diameter of the cover is approximately thesame size as an outer diameter of the support frame.

The cover can be positioned over the outer surface of the support frame.For example, the cover can be stretched slightly to allow the supportframe to be placed within the cover. Alternatively, the outer diameterof the tubular frame could be enlarged so as to place the cover aroundthe outer surface of the support frame. Other ways of placing the coveraround the outer surface of the support frame are also possible,including placing the cover around both the inside and the outside ofthe frame.

In one embodiment, the cover can be positioned over and attached to thesupport frame so that the cover extends between the convex curves of thesecond end member to form the valve leaflets. For example, the supportframe includes the first convex curve and the second convex curve alongthe second end member. Providing cover over the support frame then formsthe first valve leaflet and the second valve leaflet of the cardiacvalve.

As discussed herein, the cover can also be trimmed along the first endmember so as to define the open area between the sequence of convexcurves and concave curves along the first end member. Alternatively, thecover can include a first end having a series of convex and concavecurves that correspond to those of the first end member so as to providethe open area.

In an additional embodiment, the cardiac valve can be formed byproviding support frame and cover, where the second end member ofsupport frame includes the first convex curve, the second convex curve,and the third convex curve. Cover can include cylindrical shape that hasa second end having a predetermined shape that allows for the formationof the valve leaflets of the tri-leaflet cardiac valve. The second endcan also include arcuate edges each having the optional nodularinterruption. The cover further includes concave surfaces, as describedherein, which can be imparted into the cover through any number ofmanufacturing processes, including, but not limited to, thermo-molding,heat setting, and chemical cross-linking. As discussed herein, thisexample of the cover permits the valve leaflets to be created once thecover is properly positioned on the support frame.

As discussed herein, the cover can also be positioned over both theouter surface and the inner surface of the support frame. For example,two covers can be positioned on the support frame to provide anembodiment of the cardiac valve, or a longer cover can be used over thesupport frame. In addition, additional material can be positionedbetween the two covers at least in the area between the convex andconcave curves of the second end member.

In addition, one or more flexible support ribs having a predeterminedshape could also be incorporated into the cover in forming the concavesurfaces. As discussed herein, the cover configuration having thearcuate edges, nodular interruptions, and the concave surfaces permitsthe valve leaflets to be created once the cover is properly positionedover the support frame. The cover can then be affixed to the supportframe and itself as discussed herein.

The cover can also be trimmed along the first end member so as to definethe open area between the sequence of convex curves and concave curvesalong the first end member. Alternatively, the first end of cover caninclude a series of convex and concave curves that correspond to thoseof the first end member so as to provide the open area.

In an additional embodiment, surfaces defining the opening through oraround the cover can also be provided on the cardiac valve. The tubularmember can then be coupled in fluid tight communication to the openingto provide fluid communication with the opening around or through thecover. In one embodiment, the first end of the tubular member can becoupled to the support frame with the opening and the lumen of thetubular member aligned so that fluid can move through the opening andthe tubular member once the valve has been implanted in a patient.Alternatively, the tubular member can be positioned in the patient,independent of the valve and then subsequently coupled to the valve oncethe valve has been implanted in the patient.

As discussed herein, the tubular member allows for the valve to bepositioned in any number of locations within the vasculature while stillallowing fluid communication with adjacent physiological structures. Forexample, valve could be implanted in the aorta of a patient downstreamof the coronary ostia. In order to provide sufficient blood supply tothe coronary ostia, the tubular member can be positioned with the secondend of the tubular member in the coronary ostia so as to supply arterialblood at arterial pressures to the coronary arteries.

FIG. 5 illustrates one embodiment of a system 509. System 509 includesvalve 500, as described herein, reversibly joined to a delivery catheter511. The delivery catheter 511 includes an elongate body 513 having aproximal end 515 and a distal end 517, where valve 500 can be locatedbetween the proximal end 515 and distal end 517. The delivery catheter511 can further include a lumen 519 longitudinally extending to thedistal end 517. In one embodiment, lumen 519 extends between proximalend 515 and distal end 517 of catheter 511. The catheter 511 can furtherinclude a guidewire lumen 521 that extends within the elongate body 513,were the guidewire lumen 521 can receive a guidewire for positioning thecatheter 511 and the valve 500 within a body lumen (e.g., the aorta of apatient).

The system 509 can further include a deployment shaft 523 positionedwithin lumen 519, and a sheath 525 positioned adjacent the distal end517. In one embodiment, the valve 500 can be positioned at leastpartially within the sheath 525 and adjacent the deployment shaft 523.The deployment shaft 523 can be moved within the lumen 519 to deployvalve 500. For example, deployment shaft 523 can be used to push valve500 from sheath 525 in deploying valve 500.

FIG. 6 illustrates an additional embodiment of the system 609. Thecatheter 611 includes elongate body 613, lumen 619, a retraction system627 and a retractable sheath 629. The retractable sheath 629 can bepositioned over at least a portion of the elongate body 613, where theretractable sheath 629 can move longitudinally along the elongate body613. The valve 600 can be positioned at least partially within theretractable sheath 629, where the retractable sheath 629 moves along theelongate body 613 to deploy the valve 600. In one embodiment, retractionsystem 627 includes one or more wires 699 coupled to the retractablesheath 627, where the wires 699 are positioned at least partially withinand extend through lumen 619 in the elongate body 613. Wires 699 of theretraction system 627 can then be used to retract the retractable sheath629 in deploying valve 600.

FIG. 7 illustrates an additional embodiment of the system 709. Thecatheter 711 includes elongate body 713, an inflatable balloon 731positioned adjacent the distal end 717, and a lumen 735 longitudinallyextending in the elongate body 713 of the catheter 711 from theinflatable balloon 731 to the distal end 717. In the present example,the inflatable balloon 731 can be at least partially positioned withinthe lumen 726 of the valve 700. The inflatable balloon 731 can beinflated through the lumen 735 to deploy the valve 700.

The embodiments of the present invention further include methods forforming the valve of the present invention, as discussed herein. Forexample, the valve can be formed from the support frame and the coverover at least the outer surface of the support frame, where the coverincludes surfaces defining the reversibly sealable opening forunidirectional flow of a liquid through the lumen. In an additionalexample, the valve can be reversibly joined to the catheter, which caninclude a process of altering the shape of the valve from a first shape,for example an expanded state, to the compressed state, as describedherein.

For example, the valve can be reversibly joined with the catheter bypositioning valve in the compressed state at least partially within thesheath of the catheter. In one embodiment, positioning the valve atleast partially within the sheath of the catheter includes positioningthe valve in the compressed state adjacent the deployment shaft of thecatheter. In another embodiment, the sheath of the catheter functions asa retractable sheath, where the valve in the compressed state can bereversibly joined with the catheter by positioning the valve at leastpartially within the reversible sheath of the catheter. In a furtherembodiment, the catheter can include an inflatable balloon, where theballoon can be positioned at least partially within the lumen of thevalve, for example, in its compressed state.

The embodiments of the valve described herein may be used to replace,supplement, or augment valve structures within one or more lumens of thebody. For example, embodiments of the present invention may be used toreplace an incompetent cardiac valve of the heart, such as the aortic,pulmonary and/or mitral valves of the heart.

In one embodiment, the method of replacing, supplementing, and/oraugmenting a valve structure can include positioning at least part ofthe catheter including the valve at a predetermined location within anartery of a patient, such as in the aorta adjacent the root of theaortic valve. In positioning the valve of the present invention withinthe aorta, particular physiological structures need to be taken intoconsideration. For example, the valve of the present invention works inconjunction with the coronary artery ostia much in the same way as thenative aortic valve. This is accomplished due to the configuration ofboth the support frame and the cover of the valve as described herein.

For example, the configuration of the valve of the present inventionpermits the valve to be implanted such that the support frame can bepositioned between the native aortic valve and the coronary arteryostia. As discussed herein, the open area defined by the support frameallows the valve to be seated adjacent the native aortic valve. Inaddition, the valve leaflets of the present invention can be in the samerelative position as the native valve leaflets. This allows the valveleaflets of the present invention to interact with the coronary ostiapositioned in the aortic sinuses (sinuses of Valsalva) adjacent theaortic valve in the similar manner as the native valve leaflets. So, thevalve of the present invention can properly accommodate both the aorticvalve and the coronary ostia.

In one embodiment, positioning the catheter including the valve withinthe body lumen includes introducing the catheter into the cardiovascularsystem of the patient using minimally invasive percutaneous,transluminal catheter based delivery system, as is known in the art. Forexample, a guidewire can be positioned within the cardiovascular systemof a patient that includes the predetermined location. The catheter,including valve, as described herein, can be positioned over theguidewire and the catheter advanced so as to position the valve at oradjacent the predetermined location. In one embodiment, radiopaquemarkers on the catheter and/or the valve, as described herein, can beused to help locate and position the valve.

The valve can be deployed from the catheter at the predeterminedlocation in any number of ways, as described herein. In one embodiment,valve of the present invention can be deployed and placed in any numberof cardiovascular locations. For example, valve can be deployed andplaced within a major artery of a patient. In one embodiment, majorarteries include, but are not limited to, the aorta. In addition, valvesof the present invention can be deployed and placed within other majorarteries of the heart and/or within the heart itself, such as in thepulmonary artery for replacement and/or augmentation of the pulmonaryvalve and between the left atrium and the left ventricle for replacementand/or augmentation of the mitral valve. Other locations are alsopossible.

As discussed herein, the valve can be deployed from the catheter in anynumber of ways. For example, the catheter can include the retractablesheath in which valve can be at least partially housed, as discussedherein. Valve can be deployed by retracting the retractable sheath ofthe catheter, where the valve self-expands to be positioned at thepredetermined location. In an additional example, the catheter caninclude a deployment shaft and sheath in which valve can be at leastpartially housed adjacent the deployment shaft, as discussed herein.Valve can be deployed by moving the deployment shaft through thecatheter to deploy valve from the sheath, where the valve self-expandsto be positioned at the predetermined location. In an additionalembodiment, the valve can be deployed through the use of an inflatableballoon. In a further embodiment, the valve can partially self-expandupon retracting a sheath in which the valve is located, and thendeployed through the use of an inflatable balloon.

Once implanted, the valve can provide sufficient contact and expansionforce against the body lumen wall to prevent retrograde flow between thevalve and the body lumen wall, and to securely located the valve andprevent migration of the valve. For example, the valve can be selectedto have a larger expansion diameter than the diameter of the inner wallof the body lumen. This can then allow valve to exert a force on thebody lumen wall and accommodate changes in the body lumen diameter,while maintaining the proper placement of valve. As described herein,the valve can engage the lumen so as to reduce the volume of retrogradeflow through and around valve. It is, however, understood that someleaking or fluid flow may occur between the valve and the body lumenand/or through valve leaflets.

While the present invention has been shown and described in detailabove, it will be clear to the person skilled in the art that changesand modifications may be made without departing from the spirit andscope of the invention. As such, that which is set forth in theforegoing description and accompanying drawings is offered by way ofillustration only and not as a limitation. The actual scope of theinvention is intended to be defined by the following claims, along withthe full range of equivalents to which such claims are entitled.

In addition, one of ordinary skill in the art will appreciate uponreading and understanding this disclosure that other variations for theinvention described herein can be included within the scope of thepresent invention. For example, the support frame 102 and/or the cover104 can be coated with a non-thrombogenic biocompatible material, as areknown or will be known. Other biologically active agents or cells mayalso be utilized.

In the foregoing Detailed Description, various features are groupedtogether in several embodiments for the purpose of streamlining thedisclosure. This method of disclosure is not to be interpreted asreflecting an intention that the embodiments of the invention requiremore features than are expressly recited in each claim. Rather, as thefollowing claims reflect, inventive subject matter lies in less than allfeatures of a single disclosed embodiment. Thus, the following claimsare hereby incorporated into the Detailed Description, with each claimstanding on its own as a separate embodiment.

What is claimed is:
 1. A valve defining a valve lumen and comprising: aframe; a cover attached to the frame, the cover comprising: a tubularcover portion; and flaps, each flap having a variable longitudinallength and a free edge, the flaps constructed and arranged to movebetween an open state and a closed state for reversibly sealing thevalve lumen.
 2. The valve of claim 1, each flap having a second edge,the second edge extending from the tubular cover portion and attached tothe frame.
 3. The valve of claim 1, wherein the free edge extendsbetween two circumferentially adjacent convex curves of the frame. 4.The valve of claim 1, wherein the arcuate leaflet edges define a secondvalve end only when the flaps are in the open state.
 5. The valve ofclaim 1, wherein the frame has convex curves at a first frame end, eachflap extending between two convex curves.
 6. The valve of claim 1, eachflap extending across a concave area defined by a first frame end, eachflap extending over an area greater than the concave area.
 7. The valveof claim 1, the frame having a longitudinal frame length and a framediameter, the valve further comprising a hollow elongate tubular member,the tubular member having a longitudinal tubular member length greaterthan the longitudinal frame length, and a tubular member diameter lessthan the frame diameter.
 8. The valve of claim 1, wherein each flap is asingle layer of cover material.
 9. A valve comprising: a frame having alongitudinal frame length measured from a first frame end to a secondframe end, the longitudinal frame length being uniform, the framedefining a first valve end; a cover engaged to an outer surface of theframe, the cover including leaflets movable relative to the frame,wherein when the valve is open the cover has a variable longitudinalcover length comprising: minimum longitudinal cover lengths equal to thelongitudinal frame length, and maximum longitudinal cover lengthsgreater than the longitudinal frame length, each minimum longitudinalcover length is positioned between two maximum longitudinal coverlengths, and each maximum longitudinal cover length is positionedbetween two minimum longitudinal cover lengths, and a number oflocations with the maximum longitudinal cover length is equal to anumber of the leaflets.
 10. The valve of claim 9, wherein the leafletsare flaps of the cover.
 11. The valve of claim 9, the cover furtherengaged to an inner surface of the frame, wherein the leaflets comprisetwo layers of the cover.
 12. A valve comprising: a tubular frame with afirst frame end comprising convex curves and concave curves, eachconcave curve having a maximum depth and extending between two convexcurves; and flaps for regulating flow through the tubular frame, whereineach flap extends across an area defined between two circumferentiallyadjacent convex frame portions and has a maximum longitudinal lengthgreater than the maximum depth of the concave curve.
 13. The valve ofclaim 12, wherein each flap has a variable longitudinal length.
 14. Thevalve of claim 12, the flaps having a free edge, wherein the free edgesform a first valve end when the valve is in an open state, and the firstframe end forms the first valve end when the valve is in a closed state.15. The valve of claim 12, each flap having a curved free edge curvinglongitudinally outward from the two circumferentially adjacent convexframe portions when the valve is in the open configuration.
 16. Thevalve of claim 15, wherein the curved free edge extends radially inwardwhen the valve is in the closed configuration.
 17. The valve of claim12, wherein the valve has a greater longitudinal length when theleaflets are open than when the leaflets are closed.
 18. The valve ofclaim 12, the tubular frame defining a lumen with a diameter, whereinwhen the valve is in a closed configuration, the flaps extend across thediameter of lumen.
 19. The valve of claim 18, each flap having a sideattached to the first frame end, a free edge, and a major surfacebetween the side and the free edge, wherein when the valve is in aclosed configuration the major surface has a concave shape.
 20. Thevalve of claim 12, wherein when the valve is in an open configurationeach flap is semi-tubular.